Figure 3.

¹³C distribution in first turn of the Krebs cycle with [¹³C₅]- or [¹³C-1,5]glutamine. A, [¹³C₅]glutamine (red circles) enters the cycle and distributes as M + 4 isotopologues through oxidative glutaminolysis (inside of cycle) or M + 5 citrate through reductive carboxylation (outside of cycle). Striped dots represent labeled carbons from [¹³C₃]pyruvate produced via malic enzyme re-entering the Krebs cycle. For simplicity, not all isotopologues are shown, and the re-entry of labeled pyruvate into the Krebs cycle could produce the same isotopologues as in Fig. 2A. B, labels from [¹³C-1]Gln (red circles) are lost following decarboxylation of C-1 by α-KG dehydrogenase. The ¹³C label is retained in citrate through the reverse reaction of IDH but is not incorporated into fatty acids. The label from [¹³C-5]Gln (blue circle) is retained through glutaminolysis but is only incorporated into fatty acids via reductive carboxylation.